Evaluating the impact of grain boundaries on the functional properties of CdTe thin films, consistent with processes used in photovoltaic solar cells, requires a direct correlation between their crystallography and electronic behavior. In the present work, we propose a novel comprehensive approach, combining focused ion beam/electron backscatter diffraction tomography (3D-EBSD) and quantitative cathodoluminescence (CL). While the former enables a full five parameter characterization of the interfaces, the latter is used to probe the spatial distribution of recombination centers and their characteristics. In addition, critical issues associated with sample preparation are also discussed. Monte Carlo simulations, together with electron channeling contrast imaging (ECCI), are employed to evaluate the effects of ion-sputtering damage on the CL response of CdTe thin films, as well as to overcome the resolution limit of EBSD characterization. The results obtained show that, at the exception of coherent twin boundaries, all interfaces behave as non-radiative recombination centers, exhibiting significant recombination velocities. Furthermore, there is no direct correlation between the misorientation parameters of the interfaces and their recombination properties. In contrast, trends can be observed when considering the crystallography of the boundary planes.